Picolinic acid based Cu(II) complexes with heterocyclic bases--crystal structure, DNA binding and cleavage studies.

Autor: Pulimamidi RR; Department of Chemistry, Osmania University, Hyderabad 500007, India. Electronic address: rabi_pr@rediffmail.com., Nomula R; Department of Chemistry, Osmania University, Hyderabad 500007, India., Pallepogu R; School of Chemistry, University of Hyderabad, Hyderabad 500046, India., Shaik H; Department of Chemistry, Osmania University, Hyderabad 500007, India.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2014 May 22; Vol. 79, pp. 117-27. Date of Electronic Publication: 2014 Apr 01.
DOI: 10.1016/j.ejmech.2014.03.084
Abstrakt: In view of the importance of picolinic acid (PA) in preventing cell growth and arresting cell cycle, new PA based metallonucleases were designed with a view to study their DNA binding and cleavage abilities. Three new Cu(II) complexes [Cu(II)(DPPA)].4H2O (1),[Cu(II)(DPPA)(bpy)].5H2O (2) and [Cu(II)(DPPA)(phen)].5H2O (3), were synthesized using a picolinic acid based bifunctional ligand (DPPA) and heterocyclic bases (where DPPA: Pyridine-2-carboxylic acid {2-phenyl-1-[(pyridin-2-ylmethyl)-carbonyl]-ethyl}-amide; bpy: 2, 2'-bipyridine and phen: 1, 10-phenanthroline). DPPA was obtained by coupling 2-picolinic acid and 2-picolyl amine with l-phenylalanine through amide bond‌‌. Complexes were structurally characterized by a single crystal X-ray crystallography. The molecular structure of 1 shows Cu(II) center essentially in a square planar coordination geometry, while complex 2 shows an approximate five coordinated square-pyramidal geometry. Eventhough we could not isolate single crystal for complex (3), its structure was established based on other techniques. The complex (3) also exhibits five coordinate square pyramidal geometry. The complexes show good binding affinity towards CT-DNA. The binding constants (Kb) decrease in the order 1.35 ± 0.01 × 10(5) (3) > 1.23 ± 0.01 × 10(5) (2) > 8.3 ± 0.01 × 10(4) (1) M(-1). They also exhibit efficient nuclease activity towards supercoiled pUC19 DNA both in the absence and presence of external agent (H2O2). The kinetic studies reveal that the hydrolytic cleavage reactions follow the pseudo first-order rate constant and the hydrolysis rates are in the range of (5.8-8.0) × 10(7) fold rate enhancement compared to non-catalyzed double stranded DNA (3.6 × 10(-8) h(-1)).
(Copyright © 2014 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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